Unterschiedliche Beeinflußbarkeit der Noradrenalin- und Isoprenalinwirkungen am isolierten Meerschweinchenvorhof

Summary

The actions of noradrenaline and isoprenaline on isolated guinea pig atria have been analyzed by a study of the modification by various drugs of the responses to these catechol amines. Drugs used were cocaine, reserpine, phenoxybenzamine, guanethidine, tyramine, hexamethonium and nialamide. While pretreatment with reserpine or nialamide had no detectable influence on the responses of the atria to catechol amines, the exposure of normal atria or of atria obtained from reserpine-treated animals to cocaine, guanethidine, phenoxybenzamine and tyramine resulted in potentiation of the responses to noradrenaline and subsensitivity to isoprenaline; hexamethonium was without influence on the responses to both catechol amines.

The antagonism between cocaine and isoprenaline had, for the concentrations studied, the character of a competitive one, cocaine causing a parallel shift of the dose-response curve to the right; as was expected, the same concentrations of cocaine potentiated noradrenaline, shifting the dose-response curve to the left. Although in opposite senses, cocaine shifted the curves roughly by the same distance.

In higher concentrations, cocaine depressed also the responses to noradrenaline; when added to the bath during the action of noradrenaline or isoprenaline, cocaine induced a faster termination of the stimulant effects of the catechol amines.

Cocaine somewhat antagonized the responses of the atria to histamine, but not in the same degree as those to isoprenaline.

The results are discussed in the light of present knowledge about the mechanism of supersensitivity to noradrenaline due to cocaine. It is concluded that it is not mandatory to accept two different sets of cardiac β-receptors (one activated by noradrenaline, another by isoprenaline) in order to explain the results obtained. Cocaine probably influences in two ways the cardiac actions of catechol amines, preventing their uptake by tissues and antagonizing their actions at the level of the receptors, the first action resulting in an increase of the concentration of the agonist drug. The overall effect should be supersensitivity to amines whose action is predominantly terminated by uptake (like noradrenaline) and subsensitivity to amines which are not, or only in a minor degree, taken up by tissues (like isoprenaline); higher concentrations of cocaine should be able to reduce the responses to all amines. This working hypothesis agrees fairly well with the referred results.